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Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.
- Source :
-
American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2011 Jun; Vol. 300 (6), pp. G956-67. Date of Electronic Publication: 2011 Mar 31. - Publication Year :
- 2011
-
Abstract
- Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.
- Subjects :
- Analysis of Variance
Animals
Biomarkers blood
Blood Glucose metabolism
Body Composition
Diet, Protein-Restricted
Dietary Fats administration & dosage
Dietary Fats metabolism
Endoplasmic Reticulum pathology
Energy Intake
Fatty Acids, Nonesterified blood
Fatty Liver genetics
Fatty Liver metabolism
Fatty Liver pathology
Fatty Liver physiopathology
Gene Expression Regulation
Glucose Intolerance etiology
Glucose Intolerance metabolism
Inflammation genetics
Inflammation metabolism
Inflammation pathology
Inflammation physiopathology
Inflammation Mediators metabolism
Insulin blood
Insulin Resistance
Liver pathology
Liver physiopathology
Magnetic Resonance Spectroscopy
Male
Mice
Mice, Inbred C57BL
Oxidation-Reduction
PPAR gamma genetics
PPAR gamma metabolism
Time Factors
Triglycerides blood
Unfolded Protein Response
Animal Nutritional Physiological Phenomena
Diet, Carbohydrate-Restricted adverse effects
Diet, Ketogenic adverse effects
Endoplasmic Reticulum metabolism
Fatty Liver etiology
Inflammation etiology
Liver metabolism
Stress, Physiological
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1547
- Volume :
- 300
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Gastrointestinal and liver physiology
- Publication Type :
- Academic Journal
- Accession number :
- 21454445
- Full Text :
- https://doi.org/10.1152/ajpgi.00539.2010